Ghrelin, via corticotropin-releasing factor receptors, reduces glucose uptake and increases lipid content in mouse myoblasts cells.

Michal Elbaz, Eran Gershon

Physiological reports 2021 Jan

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Ghrelin and the corticotropin-releasing factor (CRF) family are known regulators of cellular metabolism and energy balance. We previously demonstrated that myoblast glucose metabolism is regulated by ghrelin and that this effect is mediated by CRF receptor type 2 (CRF-R2). Here we explored the effect of des-acyl ghrelin, the major circulating isoform of ghrelin, on cellular metabolism in mouse myoblast C2C12 cells, and examined whether CRF family receptors mediate its metabolic effects in muscle cells. C2C12 cells were exposed to des-acyl ghrelin with or without the CRF-R1- and CRF-R2-specific antagonists antalarmin or antisauvagine-30, respectively. Des-acyl ghrelin reduced glucose uptake and expression of the glucose transporter GLUT4, but induced retinol-binding protein 4 (RBP4) expression. Antalarmin and antisauvagine-30 inhibited the induction of glucose uptake by des-acyl ghrelin and its effect on GLUT4 and RBP4 expression. Moreover, treating C2C12 cells with des-acyl ghrelin resulted in cAMP activation in response to the CRF-R1-specific ligand stressin, and the CRF-R2-specific ligand Ucn3. Furthermore, des-acyl ghrelin reduced the expression of uncoupling proteins UCP2 and UCP3. Adding antalarmin or antisauvagine-30 to the medium reversed this effect. Finally, des-acyl ghrelin elevated lipid content and acetyl-CoA carboxylase expression in C2C12 cells. Our results suggest that during food deprivation, des-acyl ghrelin signals the muscle cells that glucose levels are low and that they should switch to fatty acids for their metabolic fuel. © 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Citation

Michal Elbaz, Eran Gershon. Ghrelin, via corticotropin-releasing factor receptors, reduces glucose uptake and increases lipid content in mouse myoblasts cells. Physiological reports. 2021 Jan;9(2):e14654